Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

Kidney Int. 2018 Dec;94(6):1151-1159. doi: 10.1016/j.kint.2018.06.031. Epub 2018 Oct 6.


Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. This was associated with increased glomerular lipid droplets and cholesterol crystals. Treatment of mice with Alport Syndrome with hydroxypropyl-β-cyclodextrin (HPβCD) reduced cholesterol content in the kidneys of mice with Alport Syndrome and protected from the development of albuminuria, renal failure, inflammation and tubulointerstitial fibrosis. Cholesterol efflux and trafficking-related genes were primarily affected in mice with Alport Syndrome and were differentially regulated in the kidney cortex and isolated glomeruli. HPβCD also protected from proteinuria and mesangial expansion in a second model of non-metabolic kidney disease, adriamycin-induced nephropathy. Consistent with our experimental findings, microarray analysis confirmed dysregulation of several lipid-related genes in glomeruli isolated from kidney biopsies of patients with primary FSGS enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in non-metabolic glomerular disorders such as Alport Syndrome and FSGS, and HPβCD improves renal function in experimental Alport Syndrome and FSGS.

Keywords: Alport syndrome; FSGS; cholesterol metabolism; hydroxypropyl beta cyclodextrin; renal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / pharmacology
  • 2-Hydroxypropyl-beta-cyclodextrin / therapeutic use*
  • Animals
  • Autoantigens / genetics
  • Biopsy
  • Cholesterol / metabolism
  • Collagen Type IV / genetics
  • Doxorubicin / toxicity
  • Female
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Kidney Glomerulus / pathology*
  • Lipid Metabolism / drug effects
  • Mice
  • Mice, Knockout
  • Nephritis, Hereditary / drug therapy*
  • Nephritis, Hereditary / genetics
  • Nephritis, Hereditary / metabolism
  • Nephritis, Hereditary / pathology
  • Observational Studies as Topic


  • Autoantigens
  • Collagen Type IV
  • type IV collagen alpha3 chain
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Doxorubicin
  • Cholesterol